The Mayo Clinic Alzheimer's Disease Patient Registry (ADPR) was developed in response to an RFA from NIA. Our ADPR provides longitudinal data which focus on epidemiological, clinical, neuropsychological, and pathological features of patients with dementia, and identifies those fulfilling the criteria of AD. There are two major components to this program. The "retrospective" approach utilizes the comprehensive medical records-linkage system at Mayo Clinic for the population of Rochester, Minnesota, and has identified more than 1200 dementia incidence cases over the 25-year period, 1960-1984. This component provides the only longitudinal incidence rates in North America. Numerous risk factors are being evaluated by comparing the incidence cases with age- and sex-matched controls from the community registry. Recent data from this project indicate that the incidence rates of AD may be increasing in the population 85 years and older. The ADPR "prospective" study has enrolled and is currently following over 250 pairs of dementia patients and their age- and sex-matched controls. This project provides information on the natural history of AD, as well as data useful for improving diagnostic techniques. The normal control cohort in this prospective study has also contributed to the development of a normative data base on several common neuropsychological tests for individuals aged 55 to 100 years. Our clinical and pathological comparisons for those 85 years and older in this cohort demonstrate that additional research to establish the boundaries between dementia and normal aging is needed. Having attained many of our objectives in the current project, we now propose new specific aims arising from our registry experience, designed to capitalize on the maturity of this data resource. These fall into four general areas: 1) to continue incidence, prevalence, and case-control studies to determine if the apparent increase in the incidence rate for AD in the old-old (85 + years) is not an artifact and, if not, to explore the reason(s) for the increase; 2) to determine the incidence and prevalence rates of vascular dementia based on recently published diagnostic criteria; 3) to prospectively study the natural history of AD in its late stages; and 4) to define cognitive, functional, and neuropathological boundaries between normal aging and early AD in the old-old. In addition, we will continue our case-control evaluations of putative etiologic factors, including the hypothetical association between autoimmune disease and AD. We will also continue our program in normative neuropsychology research and attempt to develop a screening method for detecting psychiatric comorbidity in community-dwelling dementia patients. Finally, consistent with the original goal of AD registries, we will continue to serve investigators within and outside the Mayo Clinic as a resource for subjects, tissues, and data from a clinically well-characterized cohort of dementia patients.